Duloxetine for Generalized Anxiety Disorder Treatment

Mechanism of Action and Efficacy

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that inhibits the presynaptic reuptake of both neurotransmitters in the brain, as recommended by the American Academy of Child and Adolescent Psychiatry 1, 2
Despite norepinephrine's association with the stress response and anxiety generation, SNRIs have demonstrated efficacy in treating anxiety disorders, likely due to complex interactions with other neurotransmitters, according to the American Academy of Child and Adolescent Psychiatry 2
Duloxetine is the only SNRI with FDA indication specifically for GAD treatment in both adults and children/adolescents (7 years and older), as stated by the American Academy of Child and Adolescent Psychiatry 2

Most common treatment-emergent adverse effects include nausea, dizziness, dry mouth, constipation, somnolence, and headache, as reported by the American Academy of Child and Adolescent Psychiatry 3, 4
Adverse effects such as nausea can be reduced by starting at a lower dose (30 mg) for the first week before increasing to 60 mg, as recommended by the Mayo Clinic 4
SNRIs including duloxetine have been associated with increased blood pressure and pulse, requiring monitoring, according to the American Academy of Child and Adolescent Psychiatry 3
Concomitant administration of duloxetine with MAOIs is contraindicated due to increased risk of serotonin syndrome, as warned by the American Academy of Child and Adolescent Psychiatry 3
Duloxetine may interact with drugs metabolized by CYP1A2 and CYP2D6, and use with caution is advised in patients receiving drugs extensively metabolized by CYP2D6, particularly those with narrow therapeutic index, as cautioned by the American Academy of Child and Adolescent Psychiatry and the Mayo Clinic 3, 4

Duloxetine has a sufficiently long elimination half-life (approximately 12 hours) to permit once-daily dosing, as reported by the American Academy of Child and Adolescent Psychiatry 3
Unlike some other antidepressants, duloxetine does not appear to produce clinically important electrocardiographic changes, as noted by the Mayo Clinic 4
A discontinuation syndrome has been reported following missed doses or abrupt discontinuation, and a slow tapering schedule over at least 2 weeks is recommended when discontinuing treatment, as advised by the American Academy of Child and Adolescent Psychiatry 3